This is a response to RFA # RFA-AG-09-002. The major goals of the proposal are to: (1) Identify biomarkers that are associated with progression from normal cognitive status to mild cognitive impairment (MCI) or dementia, with a particular focus on the dementia of Alzheimer's disease (AD) - these biomarkers may potentially include measures based on cognitive testing, magnetic resonance imaging (MRI), blood, or cerebrospinal fluid (CSF); (2) Determine which cross-sectional or longitudinal biomarker measures (taken alone or in combination) are the best predictors of progression from normal cognition to varying levels of cognitive dysfunction (i.e., MCI or AD); (3) Create a publicly accessible data base containing the clinical, cognitive, imaging, blood and CSF data - raw imaging data and samples of blood and CSF will also be available to investigators in the field, as appropriate. A team of investigators has been assembled at the study site with substantial experience in the clinical evaluation of older individuals, as well as expertise in the analysis of the biomarkers in question. Several external advisory groups will be assembled in order to provide guidance concerning the analysis of the data (particularly the CSF and blood samples, which are a non-renewable resource). In order to accomplish these goals we will: (1) complete a comprehensive clinical evaluation on as many prior participants in BIOCARD as possible in order to determine their current clinical and cognitive status - this will represent an approximate 10 year follow-up of the cohort; (2) initiate annual, longitudinal, clinical and cognitive evaluations on as many of these individuals as possible in order to complete a 15 year follow-up of the cohort by the end of the funding period; (3) complete analyses of the previously collected MRI scans, CSF samples and blood, using state-of-art techniques; (4) complete analyses of the relationship of the previously collected data to the current status of the subjects; and (5) provide these data to the scientific community through a publicly accessible database. RELEVANCE: The aim of this study is to examine measures that might be helpful in identifying normal individuals at risk for progression to mild or moderate cognitive impairment.